Deanna: rituxan

August 28, 2004

(Rituximab)

Rituxan is a monoclonal antibody approved by the FDA in November 1997 for use in the treatment of mild cases of B-cell non-Hodgkin Lymphoma (NHL), a type of cancer. It is still in the experimental stage for treating ITP, however initial results are encouraging.

Rituxan reduces the number of B cells in your body. B cells are a type of white blood cell that, when activated, multiply and produce antibodies. Since Rituxan reduces the number of B cells it reduces the number of cells that produce antibodies including the antibodies that attack platelets. Antibody production is triggered by antigens. An antigen and antibody fit together like a key in a lock. When an antigen and antibody key and lock are joined in a B cell the body eliminates it since that B cell's work is done.

CD20 is the name of one antigen that is closely associated with B cells. Rituxan is made up of antibody keys that fit the CD20 lock. When Rituxan attaches to B cells that include CD20 the body eliminates the B cells as it would any B cells that have antibodies linked to antigens and have served their purpose. If the eliminated B cells were the ones that were producing the anti-platelet antibodies they are eliminated as well. Note that the B cells that are eliminated are not specific B cells that target cancer or ITP. Rituxan reduces the general population of all B cells with a CD20 receptor. It could take up to a year for someone to replace those B cells and have their immune system and antibody production (including the helpful antibodies) back in working order.

Dosage

The dose in the ITP study is 375 mg/m2 once weekly for four weeks. The package insert warns that Rituxan is not to be given in a single dose as an IV push and that "patients with pre-existing cardiac and pulmonary conditions or those with prior clinically significant cardiopulmonary adverse events should be monitored during and after subsequent infusions."

Rituxan is a sterile, clear, colorless, preservative-free liquid concentrate for intravenous (IV) administration. Hypersensitivity reactions may occur, and the manufacturer recommends premedication with acetaminophen (Tylenol) and diphenhydramine (Benadryl) before each infusion.

Side Effects

Adverse effects were reported in 87% of the patients. Ten percent of patients reported very serious adverse effects. These adverse effects include, fever, chills, weakness, nausea and headaches.

In December 1998, the manufacturer Genentech, Inc. and IDEC Pharmaceuticals Corporation came out with a warning to inform the public that eight deaths had occurred associated with the use of Rituxan. These adverse events represent an increase in the severity of infusion-related symptoms. Since its approval in November 1997, to December 1998, approximately 70 cases of serious infusion-related events had been reported out of an estimated 12,000 to 14,000 patients that had been treated with Rituxan worldwide.

New FDA Warning (May 8, 2001) " There were 20 post-marketing reports of severe mucocutaneous reactions associated with the use of RITUXAN in an extimated 100,000 patients since product launch. Eight of these resulted in fatal outcomes..." Contact RITUXAN Medical Information Department at 1- if you have any questions.

Related Web Sites

http://www.itppeople.com/clinical.htm (Clinical Trials Page)

http://www.rituxan.com/

http://www.idecpharm.com/

http://www.gene.com/

http://www.cancerresearch.org/anti98/grillo.html

http://www.athensnewspapers.com/1997/112797/1127.a3fda.html